P-027: SICKLE CELL DISEASE AND AUTOIMMUNE LIVER DISORDERS: SHOULD HEMATOPOIETIC STEM CELL TRANSPLANTATION BE DISCUSSED EARLY?
Authors: LACAILLE F., ALLALI S., TAYLOR M., CASTELLE M., REBEUH J., NEVEN B., PAILLARD C., DE MONTALEMBERT M.
Journal: HemaSphere (2022)

Purpose: Patients with sickle cell disease (SCD) are prone to dys- or autoimmune disorders, such as autoimmune hepatitis (AIH), sclerosing cholangitis, or ulcerative colitis. Sclerosing cholangitis can develop in young children with an unusually severe course due to associated vaso-occlusion and ischemia. Liver transplantation may be indicated early but is a challenging procedure in SCD, with uncertain outcomes (Hurtova Liver Transpl 2011, Duvoux [abstract] JFHOD 2021). Hematopoietic stem cell transplantation (HSCT) can cure SCD, although conditioning may induce hepatic complications. Herein we report a series of 6 children with SCD and autoimmune disorders, 3 for whom liver or digestive symptoms resolved after successful HSCT, and 3 for whom cirrhosis precluded HSCT conditioning. Materials and methods: Of the 6 children (5 girls), 5 were HbSS and 1 was HbSC. Dysimmune symptoms appeared at a median age of 4.5 (3-12) years and were colitis (n=2), cerebral vasculitis (n=1), and AIH (n=3). In 4/6 patients, liver disease was an overlap AIH-sclerosing cholangitis, while 2/6 patients had either isolated AIH or sclerosing cholangitis. Liver biopsy showed cirrhosis in 3 patients. Median age at last follow-up (FU) was 13.5 (8-17) years. Results: The 3 patients without cirrhosis, including 2 with sclerosing cholangitis and dilated bile ducts, underwent HSCT with a geno-identical donor, at 6, 11.5 and 16 years old. Autoimmune disease was controlled with steroids, azathioprine, infliximab or cyclophosphamide with plasma exchanges and rituximab. Conditioning included hepatotoxic drugs busulfan (n=2) and treosulfan (n=1), with antilymphocyte globulins, fludarabine (n=3) and thiotepa (n=1). Transient hepatitis developed in 1 patient and moderate graft-vs-host disease (GVHD) in 2, which resolved after adapting immunosuppression treatment. HSCT was uneventful in the third patient. With a FU of 1 to 2.5 years, all 3 patients had no digestive or liver symptoms, normal or mildly elevated liver enzymes and unchanged liver imaging. The 3 patients with cirrhosis upon first visit, at ages 7, 8.5, 13 years old, were on regular exchange transfusions at last FU. One patient developed recurrent infectious cholangitis and received a liver transplant at age 10, with many complications; at 7 years of FU, sclerosing cholangitis relapsed and re-transplantation was discussed. Another had moderate portal hypertension, bilirubin levels of 100-200 µM, and prothrombin time 60%, on steroids. The third patient was on tacrolimus, had presented 2 episodes of reversible liver failure, bilirubin levels of 100 µM and prothrombin time 45% at last FU and had developed myasthenia. Conclusion: Autoimmune liver disease in children with SCD may rapidly lead to end-stage liver disease. Upon diagnosis, these disorders should be considered as severe complications of SCD and prompt early discussion of HSCT. HSCT should be performed before conditioning with hepatotoxic drugs is not feasible. If a geno-identical donor is not available, alternative donors could be considered (haplo-identical, unrelated). If the liver disease is not stabilized after HSCT, liver transplantation could be performed with a standard risk, in a patient rid of SCD. If liver transplantation must be performed before HSCT, HSCT could be discussed rapidly afterwards to avoid possible relapse of SCD-related liver disease and dysimmune liver disease. The authors do not declare any conflict of interest